title: The tumor marker human placental protein 11 is an endoribonuclease.
abstract: Human PP11 (placental protein 11) was previously described as a serine protease specifically expressed in the syncytiotrophoblast and in numerous tumor tissues. Several PP11-like proteins were annotated in distantly related organisms, such as worms and mammals, suggesting their involvement in evolutionarily conserved processes. Based on sequence similarity, human PP11 was included in a protein family whose characterized members are XendoU, a Xenopus laevis endoribonuclease involved in small nucleolar RNA processing, and Nsp15, an endoribonuclease essential for coronavirus replication. Here we show that the bacterially expressed human PP11 displays RNA binding capability and cleaves single stranded RNA in a Mn(2+)-dependent manner at uridylates, to produce molecules with 2',3'-cyclic phosphate ends. These features, together with structural and mutagenesis analyses, which identified the potential active site residues, reveal striking parallels to the amphibian XendoU and assign a ribonuclease function to PP11. This newly discovered enzymatic activity places PP11-like proteins in a completely new perspective.
authors.affiliation: Istituto di Biologia e Patologia Molecolari, Consiglio Nazionale delle Ricerche, Sapienza Università di Roma, Rome, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Laneve
authors.forename: Ubaldo
authors.initials: U
authors.lastname: Gioia
authors.forename: Rino
authors.initials: R
authors.lastname: Ragno
authors.forename: Fabio
authors.initials: F
authors.lastname: Altieri
authors.forename: Carmen
authors.initials: C
authors.lastname: Di Franco
authors.forename: Tiziana
authors.initials: T
authors.lastname: Santini
authors.forename: Massimo
authors.initials: M
authors.lastname: Arceci
authors.forename: Irene
authors.initials: I
authors.lastname: Bozzoni
authors.forename: Elisa
authors.initials: E
authors.lastname: Caffarelli
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002384:Catalysis; D020134:Catalytic Domain; D004722:Endoribonucleases / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011257:Pregnancy Proteins / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D012313:RNA / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000737:chemistry; D014982:Xenopus laevis
chemical_list: D014408:Biomarkers, Tumor; D011257:Pregnancy Proteins; D012330:RNA, Double-Stranded; C036270:placental protein 11; D012313:RNA; D004722:Endoribonucleases